Browse Articles
Discover research articles across all indexed journals
Rapid SNP genotyping detection method based on PCR-lateral flow dipstick detection technique
Basigin links altered skeletal stem cell lineage dynamics with glucocorticoid-induced bone loss and impaired angiogenesis
Abstract Glucocorticoid (GC) induced osteoporosis (GIOP) and osteonecrosis remain a significant health issue with few approved therapies. Here, we investigate the cellular and molecular processes by which GCs affect osteogenesis and angiogenesis. We find that GC treatment reduces bone mass through decreased bone formation by skeletal stem cells (SSCs). Concomitantly, endothelial cells increase in number but display distorted phenotypical features. Transplantation studies of SSCs combined with molecular analysis by single cell RNA-sequencing and functional testing of primary human cells tie GC-induced skeletal changes to altered stem cell differentiation dynamics. This in turn perpetuates reduced osteogenesis and vascular malformation through direct SSC-endothelial crosstalk mediated at least in part by Basigin. The genetic deletion of Basigin in the skeletal lineage as well as antibody-mediated blockade of Basigin during GC treatment prevents bone loss. Intriguingly, when administered to 2-year-old mice, anti-Basigin therapy reinstates bone remodeling to significantly improve bone mass. These findings provide therapeutic vantage points for GIOP and potentially other conditions associated with bone loss.
Substantial improvement of mechanical properties of Zn–Mg alloys to orthopedic implants via rotary swaging
CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions
Abstract Mechanical forces acting on ligand-engaged T-cell receptors (TCR) have previously been implicated in T-cell antigen recognition and ligand discrimination, yet their magnitude, frequency, and impact remain unclear. Here, we quantitatively assess forces across various TCR:pMHC pairs with different bond lifetimes at single-molecule resolution, both before and during T-cell activation, on platforms that either include or exclude tangential force registration. For this purpose, we use glass-supported lipid bilayers presenting pMHC conjugated to a molecular force sensor unit at its base, adhesion factors and costimulatory molecules to the approaching T-cells. Our results imply that CD4 + T-cell TCRs experience significantly lower forces than previously estimated, with only a small fraction of ligand-engaged TCRs being subjected to these forces during antigen scanning. These rare and minute mechanical forces do not impact the global lifetime distribution of the TCR:ligand bond. We propose that the immunological synapse is created as biophysically stable environment to prevent pulling forces from disturbing antigen recognition.
General framework of nonlinear factor interactions using bayesian networks for risk analysis applied to road safety and public health
Abstract In complex systems, understanding the nonlinear interactions among risk factors is essential for accurate risk analysis. However, traditional linear models often fail to capture these complex interdependencies, leading to significant gaps in risk prediction. The aim of this study is to present a novel approach for risk analysis of nonlinear risk interactions using Bayesian networks (BNs), thereby providing a broadly applicable method for risk management and mitigation. Specifically, this study applies a BN-based framework that integrates conditional dependencies and nonlinear effects to illustrate how multifactor risk interactions operate synergistically. Using a step-by-step approach, the interactions among multiple risk factors are first mathematically formalized, and then this framework is applied to a case study of road safety using crash report data. Additionally, a second validation case in public health (type 2 diabetes risk) is included in supplementary materials to illustrate the broader applicability of the framework. The findings demonstrate through BNs and a mathematical framework, how to analyse complex interactions more accurately than traditional methods can, revealing the amplifying or mitigating effects of individual risk factors on outcomes. This approach offers more accurate risk representations and is applicable not only to road safety but also to complex environments, such as healthcare and environmental risk analysis.
Matrix regulation: a plug-and-tune method for combinatorial regulation in Saccharomyces cerevisiae
Abstract Transcriptional fine-tuning of long pathways is complex, even in the extensively applied cell factory Saccharomyces cerevisiae. Here, we present Matrix Regulation (MR), a CRISPR-mediated pathway fine-tuning method enabling the construction of 68 gRNA combinations and screening for the optimal expression levels across up to eight genes. We first identify multiple tRNAs with efficient gRNA processing capacities to assemble a gRNA regulatory matrix combinatorially. Then, we expand the target recognition of CRISPR regulation from NGG PAM to NG PAM by characterizing dCas9 variants. To increase the dynamic range of modulation, we test 101 candidate activation domains followed by mutagenesis and screening the best one to further enhance its activation capability in S. cerevisiae by 3-fold. The regulations generate combinatorial strain libraries for both the mevalonate pathway and the heme biosynthesis pathway and increase squalene production by 37-fold and heme by 17-fold, respectively, demonstrating the versatility of our method and its applicability in fundamental research.
High sensitivity in spontaneous intracranial hemorrhage detection from emergency head CT scans using ensemble-learning approach
Synergistically competitive coordination for tailoring sodium cointercalation potential of graphite
The aggregate index of systemic inflammation is positively correlated with the risk of all-cause mortality in sepsis-associated acute kidney injury
Abstract Sepsis is a major health problem worldwide, and sepsis-associated acute kidney injury (SA-AKI) patients usually experience severe conditions, high mortality, and long length of stay. The predictive value of aggregate index of systemic inflammation (AISI) in the prognosis of several diseases has been documented. This study intends to investigate the association between AISI and mortality in SA-AKI. Data of patients with SA-AKI first admitted to the intensive care unit in 2008–2019 were acquired from the Medical Information Mart for Intensive Care IV (MIMIC-IV). The impact of AISI on 30-/90-/180-d and 1-year mortality in SA-AKI was investigated by Cox proportional hazard regression models, Kaplan-Meier analyses, and restricted cubic spline (RCS) analyses. Moreover, subgroup analyses, stratified by gender, comorbidity, and intervention, were conducted. Totally 9714 SA-AKI patients were included, and they were assigned into a Low AISI Group (AISI < 735.405 × 1018/L) and a High AISI Group (AISI ≥ 735.405 × 1018/L) based on the median of AISI. As revealed by the regression model, 30-/90-/180-d and 1-year mortality in SA-AKI was higher in the High AISI Group than in the Low AISI Group (P < 0.05). Kaplan-Meier analyses confirmed higher 30-/90-/180-d and 1-year survival rates in the Low AISI Group (Plog−rank<0.0001). Using RCS curves, we also found a nonlinear relation between AISI and 30-/90-/180-d, and 1-year mortality in SA-AKI (Pnonlinear<0.001). Subgroup analyses suggested no interaction of AISI with the stratified variables (Pinteraction>0.05), and the association of AISI with 30-d mortality was consistent across subgroups. In Conclusion, AISI has an association with mortality in SA-AKI. Quantitative stratification of AISI at admission may contribute to early detection and treatment of SA-AKI with a poor prognosis.
Revitalizing reformatsky reagent for catalyst-free direct alkylation with unactivated alkyl halides
Assessment of Chlorella vulgaris as a biological control agent against tortoise tick Hyalomma aegyptium (Acari: Ixodidae) in Egypt
Abstract Hyalomma aegyptium is a three-host tick species parasitizing mainly tortoises in Asia, North Africa, and the Middle East. It serves as a carrier for various pathogenic bacteria and protozoa that pose threats to humans, wildlife, and domestic animals. Ticks control using chemical acaricides has negative effects to the environment and animal and human health, residues in animal products and leading to resistant ticks. So safe, eco-friendly, and cost-effective methods must be alternatively used. The green microalga Chlorella vulgaris is rich in proteins, lipids, carbohydrates and vitamins. It is used in biofuel production, wastewater treatment, and as a biofertilizer. It is used in pharmaceutical drugs with many beneficial characteristics. Examination of collected specimens in the present study ensured that they were identified as H. aegyptium nymphs. Using the powdering method, nymphs were treated with Chlorella and observed for 18 days. The results showed that the effect began 4 days after treatment, the mortality percentage reached 80%, and delayed molting period with only 20% molted into males. Morphological observations using light and scanning electron microscopes revealed a stiffened nymph body after treatment with a highly damaged capitulum, integument, and legs. Integument semithin sections showed thin, disorganized cuticle with damaged layers and destructed epidermal cells after treatment. No signs of new cuticle formation were noticed. The effect of Chlorella was either mechanical through powder particles or physiological through its effect on organs. This study may provide valuable information to help in the development of new methods to control ticks and/or improve the existing ones, allowing the creation of methods which do not induce resistance in ticks, and that are less toxic to the environment and non-target organisms.
A chronic Acinetobacter baumannii pneumonia model to study long-term virulence factors, antibiotic treatments, and polymicrobial infections
Abstract Acinetobacter baumannii causes prolonged infections that disproportionately affect immunocompromised populations. Our understanding of A. baumannii respiratory pathogenesis relies on an acute murine infection model with limited clinical relevance that employs an unnaturally high number of bacteria and requires assessment of bacterial load at 24-36 h post-infection. Here, we demonstrate that low intranasal inoculums in tlr4 mutant mice allows for infections lasting at least 3 weeks. Using this “chronic infection model” we determine the adhesin InvL is a virulence factor required during later stages of infection, despite being dispensable in the early phase. We also demonstrate that the chronic model enables distinction between antibiotics that, although initially reduce bacterial burden, either lead to clearance or result in the formation of potential bacterial persisters. To illustrate how our model can be applied to study polymicrobial infections, we inoculate mice with an active A. baumannii infection with Staphylococcus aureus or Klebsiella pneumoniae. We find that S. aureus exacerbates infection, while K. pneumoniae enhances A. baumannii clearance. In all, the chronic model overcomes some limitations of the acute pulmonary model, expanding our capabilities to study A. baumannii pathogenesis and lays the groundwork for the development of similar models for other opportunistic pathogens.
Assessing the impacts of climate change and human activities on distribution of Lophatherum gracile in China using the maxent model
MacroD1 sustains mitochondrial integrity and oxidative metabolism
Abstract The mono-ADP-ribosylhydrolase MacroD1 has been recently reported to localize to mitochondria exclusively. However, the extent and means by which MacroD1 regulates metabolic homeostasis remains unclear. Here we show that the absence of MacroD1 in mice decreased mitochondrial load and negatively impacted muscle function, reducing maximal exercise capacity. Knockdown of MacroD1 in C2C12 myoblast cells amplified the production of reactive oxygen species which ultimately resulted in increased mitochondrial fission. Proteomic and metabolomic profiling showed that loss of MacroD1 re-routed metabolite flux from glucose to the pentose-phosphate cycle instead of the tricarboxylic acid cycle to support the production of antioxidants, including glutathione and NADPH. This resulted in increased glucose uptake and dependency both in vitro and in vivo. Hence, our research establishes MacroD1 as a regulator of metabolic homeostasis, which ensures the coordination of cellular carbohydrate flux and optimal mitochondrial function.
MALDI-TOF MS technique as a new approach for simultaneous detection and differentiation of potato virus Y strains
Temporal fusion of entangled resource states from a quantum emitter
Abstract Fusion-based photonic quantum computing architectures rely on two primitives: i) near-deterministic generation and control of constant-size entangled states and ii) probabilistic entangling measurements (photonic fusion gates) between entangled states. Here, we demonstrate these key functionalities by temporally fusing resource states deterministically generated using a solid-state spin-photon interface. Repetitive operation of the source leads to sequential entanglement generation, whereby curiously entanglement is created between the quantum states of the same spin at two different instances in time. Such temporal multiplexing of photonic entanglement provides a resource-efficient route to scaling many-body entangled systems with photons.